Various compounds which inhibit, or bind to, enzymes are known and have a broad range of in vitro and in vivo applications. For example, ligands immobolized to solid-phase supports which reversibly bind to enzymes are useful in affinity chromatography to purify enzymes and to separate them from biological fluids.
Among the hydrolytic enzymes are serine esterases and amidases. Juvenile hormone esterase is, for example, one of the serine esterases. Compounds which inhibit juvenile hormone esterase have received considerable interest as selective insert control agents, since juvenile hormones regulate a great number of reproductive and developmental events in insects and juvenile hormone esterase mediate the metabolism of the juvenile hormones.
Certain phosphoramidates have been found to inhibit juvenile hormone esterases. In particular, O-ethyl-S-phenyl phosphoramidothiolate (hereinafter "EPPAT") has been found to display potent in vitro inhibition of juvenile hormone esterase and topical application has been shown to disrupt development of the cabbage looper. See, e.g. Sparks and Hammock, Pestic. Biochem, Physiol. 14, 290 (1981).
Several trifluoromethylketones have recently been found to be potent inhibitors of crude juvenile hormone esterase from the cabbage looper in vitro. The most potent of these (1,1,1-trifluorotetradecan-2-one, hereinafter abbreviated "TFT") was found to display relatively greater juvenile hormone esterase activity in vitro than EPPAT. However, TFT displayed a lack of pronounced in vivo activity when applied topically to cabbage looper (Noctuidae, Trichoplusia ni). Hammock et al., Pestic. Biochem. Physiol. 17, pp. 76-88 (1982).